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Biomedical subjects

M Byrne

Publications and source records attributed to M Byrne.

At least 73 records · Page 4Linked to original sources
PubMed1999

Interleukin-1 (IL-1) inhibits growth of cytomegalovirus in human marrow stromal cells: inhibition is reversed upon removal of IL-1.

A Toledo strain cytomegalovirus (CMV) containing the gene for green fluorescent protein (GFP) under the control of elongation factor-1 promoter was used to study infection of human marrow stromal cells. Two stromal cell lines were used: HS-5, which secretes copious amounts of known cytokines and interleukins; and HS-27a, which does not secrete these activities. CMV growth and spread was monitored by counting green plaques and quantitating GFP intensity. Initial studies indicated that, whereas HS-5 and 27a have similar susceptibilities to infection, as evidenced by the same number of GFP+ cells at day 2, HS-5 appears more resistant to growth and spread of CMV. Furthermore, conditioned media from HS-5 (HS-5 CM) inhibited CMV plaque formation in HS-27a, suggesting that factors secreted by HS-5 are responsible for limiting CMV growth. Neutralizing antibodies against interleukin-1alpha (IL-1alpha) and IL-1beta completely blocked the ability of HS-5 CM to limit viral growth, suggesting that IL-1, which is known to be present in HS-5 CM, is responsible for this effect. When exogenous IL-1beta was added to CMV-infected HS-27a, both the number of plaques and the intensity of GFP was significantly reduced in IL-1-treated HS-27a compared with untreated HS-27a (the number of plaques by day 18 was 20 +/- 3 v 151 +/- 12/well, respectively; GFP intensity was 535 +/- 165 v 6,516 +/- 652/well, respectively, in 4 separate experiments). At day 21, when IL-1beta-treated, CMV-infected cultures were passaged and then cultured in the absence of IL-1beta, CMV growth progressed with the kinetics of the original untreated culture, indicating that the IL-1beta effect is reversible. Because HS-27a expresses the type I IL-1 receptor, we speculate that the antiviral effects are mediated through IL-1-induced changes in cellular gene expression. DNA chip analysis of mRNA from IL-1beta-treated and nontreated HS-27a cells has identified some candidate molecules.

Bone Marrow Cells↗
PubMed1999

Magnetic resonance imaging of brain in people at high risk of developing schizophrenia.

BACKGROUND: Schizophrenia is a multifactorial disorder that is associated with disturbed cerebral development. Structural brain-imaging studies have consistently shown that the volumes of some parts of the brain, particularly the mesial temporal lobes, are smaller in patients with schizophrenia than in healthy people. Whether these abnormalities of brain structure predate the onset of symptoms is not known. METHODS: 100 people at high risk of developing schizophrenia (two or more first-degree or second-degree relatives affected), 20 patients in their first episode of schizophrenia, and 30 healthy controls underwent magnetic resonance imaging of the brain. The volumes of regions of interest were measured by standard techniques. FINDINGS: Mean whole-brain volume was 1356 cm3 (SD 178) in the first-episode group, 1347 cm3 (122) in the high-risk group, and 1334 cm3 (149) in the controls (p=0.8). The mean volume of the left amygdala-hippocampal complex (AHC) was lower in the first-episode group (4.3 cm3 [0.6]) than in the high-risk group (4.6 cm3 [0.6]), and in turn than in the controls (4.8 cm3 [0.7]); these differences were significant (p<0.05) both for absolute volumes and values adjusted for brain volume and other confounders. The right AHC showed a similar pattern (absolute volumes 4.5 cm3 [0.7], 4.8 cm3 [0.6], 4.9 cm3 [0.9], respectively). Both thalamic nuclei were significantly smaller in the high-risk group than in the control group. INTERPRETATION: People at high risk of developing schizophrenia for genetic reasons have several structural brain abnormalities that are similar to those in patients with the disorder. If at-risk individuals with particularly small AHC or thalami are most likely to develop schizophrenia, this feature might assist in early detection and treatment.

Adolescent↗
PubMed1999

Maternal factors and the evolution of developmental mode: evolution of oogenesis in Heliocidaris erythrogramma.

Evolutionary change in developmental mode in sea urchins is closely tied to an increase in maternal provisioning. We examined the oogenic modifications involved in production of a large egg by comparison of oogenesis in congeneric sea urchins with markedly different sized oocytes and divergent modes of development. Heliocidaris tuberculata has small eggs (95 microm diameter) and the ancestral mode of development through feeding larvae, whereas H. erythrogramma has large eggs (430 microm diameter) and highly modified non-feeding lecithotrophic larvae. Production of a large egg in H. erythrogramma involved both conserved and divergent mechanisms. The pattern and level of vitellogenin gene expression is similar in the two species. Vitellogenin processing is also similar with the gonads of both species incorporating yolk protein from coelomic and hemal stores into nutritive cells with subsequent transfer of this protein into yolk granules in the developing vitellogenic oocyte. Immunocytology of the eggs of both Heliocidaris species indicates they incorporate similar levels of yolk protein. However, H. erythrogramma has evolved a highly divergent second phase of oogenesis characterised by massive deposition of non-vitellogenic material including additional maternal protein and lipid. Maternal provisioning in H. erythrogramma exhibits recapitulation of the ancestral vitellogenic program followed by a novel oogenic phase with hypertrophy of the lipogenic program being a major contributor to the increase in egg size.

Animals↗
PubMed1999

Neuropsychological assessment of young people at high genetic risk for developing schizophrenia compared with controls: preliminary findings of the Edinburgh High Risk Study (EHRS).

BACKGROUND: Finding risk indicators for schizophrenia among groups of individuals at high genetic risk for the disorder, has been the driving force of the high risk paradigm. The current study describes the preliminary results of a neuropsychological assessment battery conducted on the first 50% of subjects from the Edinburgh High Risk Study. METHODS: One hundred and four high risk subjects and 33 normal controls, age and sex matched, were given a neuropsychological assessment battery. The areas of function assessed and reported here include intellectual function, executive function, perceptual motor speed, mental control/ encoding, verbal ability and language, learning and memory measures, and handedness. RESULTS: The high risk subjects performed significantly more poorly than the control subjects in the following domains of neuropsychological function: intellectual function, executive function, mental control/encoding and learning, and memory. Controlling for IQ, high risk subjects made significantly more errors on the Hayling Sentence Completion Test (HSCT), took longer to complete section A of the HSCT, had lower scores on the delayed recall condition of the visual reproductions subtest of the Wechsler Memory Scale-Revised, and had significantly poorer Rivermead Behavioural Memory Test (RBMT) standardized scores. The presence of significant group by IQ interactions for the RBMT and time to complete section A of the HSCT suggested that differences among the groups were more marked in the lower IQ range. Performance on the HSCT was found to be related to the degree of family history of schizophrenia. CONCLUSIONS: High risk subjects performed more poorly than controls on all tests of intellectual function and on aspects of executive function and memory.

Adult↗
PubMed1999

Divergence in the chloroplast genome and nuclear rDNA of the rare western australian plant lambertia orbifolia gardner (Proteaceae)

The population genetic structure of the Australian plant Lambertia orbifolia was investigated for chloroplast DNA (cpDNA) and rDNA based on restriction fragment length polymorphism. Variation was assessed in 14-20 individuals from six populations with probes covering the majority of the chloroplast genome and the whole rRNA gene unit. For cpDNA, eight mutations were detected which were distributed over five haplotypes. Nucleotide diversity in the species was high and the majority of this diversity was distributed between populations with diversity within populations restricted to a single population. There was significant differentiation between the two regions in the species distribution with the Narrikup region being distinguished by a single haplotype that was characterized by six unique mutations. Variation in rDNA was detected with three gene length variants present in most individuals. However, the Narrikup region was characterized by homogenization of the gene unit to a single length variant in all individuals. The divergence of the Narrikup region suggests that the disjunction in the species distribution has been present for a long time and the two regions represent separate evolutionary lineages.

Journal Article↗
PubMed1999

Alpha1-antichymotrypsin-like proteins I and II purified from bovine adrenal medulla are enriched in chromaffin granules and inhibit the proenkephalin processing enzyme "prohormone thiol protease".

Proteolytic processing of inactive proenkephalin and proneuropeptides is essential for the production of biologically active enkephalins and many neuropeptides. The incomplete processing of proenkephalin in adrenal medulla suggests that endogenous protease inhibitors may inhibit proenkephalin processing enzymes. This study demonstrates the isolation and characterization of two isoforms of adrenal medullary alpha1-antichymotrypsin (ACT), referred to as ACT-like proteins I and II, which are colocalized with enkephalin in chromaffin granules and which inhibit the proenkephalin processing enzyme known as prohormone thiol protease (PTP). Subcellular fractionation demonstrated enrichment of 56- and 60-kDa ACT-like proteins I and II, respectively, to enkephalin-containing chromaffin granules (secretory vesicles). Immunofluorescence cytochemistry of chromaffin cells indicated a discrete, punctate pattern of ACT immunostaining that resembles that of [Met]enkephalin that is stored in secretory vesicles. Chromatography of adrenal medullary extracts through DEAE-Sepharose and chromatofocusing resulted in the separation of ACT-like proteins I and II that possess different isoelectric points of 5.5 and 4.0, respectively. The 56-kDa ACT-like protein I was purified to apparent homogeneity by Sephacryl S200 chromatography; the 60-kDa ACT-like protein II was isolated by butyl-Sepharose, Sephacryl S200, and concanavalin A-Sepharose columns. The proenkephalin processing enzyme PTP was potently inhibited by ACT-like protein I, with a K(i,app) of 35 nM, but ACT-like protein II was less effective. ACT-like proteins I and II had little effect on chymotrypsin. These results demonstrate the biochemical identification of two secretory vesicle ACT-like proteins that differentially inhibit PTP. The colocalization of the ACT-like proteins and PTP within chromaffin granules indicates that they could interact in vivo. Results from this study suggest that these ACT-like proteins may be considered as candidate inhibitors of PTP, which could provide a mechanism for limited proenkephalin processing in adrenal medulla.

Adrenal Medulla↗
PubMed1999

The University of Louisville Medical School's comprehensive programs to increase its percentage of underrepresented-minority students.

Since 1981, the University of Louisville (U of L) School of Medicine has developed several programs to increase the number of its underrepresented-minority (URM) matriculants and help them succeed during their medical education. The first such effort, begun in 1981, was the Professional Education Preparation Program for Kentucky high school students from underserved counties. Programs in Louisville's elementary and middle schools were initiated in 1996, and others continue through medical education and residency training. These existing supports for local URM students (most of whom are African Americans) were enhanced in 1996 by the Health Professions Partnership (HPP), a program sponsored by The Robert Wood Johnson Foundation and the Association of American Medical Colleges. With the HPP, the U of L intensified its focus on health careers preparation at the elementary and secondary education levels, and increased exchanges and collaboration between U of L health sciences faculty and teachers and students in the Jefferson Country Public Schools. Several funding sources have been used to maintain and develop the U of L's education pathway programs, including institutional, state, federal, and foundation funds. The authors describe the U of L's programs, focusing on the HPP, and state that as of 1998, the number of URM students enrolled in the U of L School of Medicine had reached almost 10% (up from 2-3% before 1993) and the graduation rate was 90%, (up from 76% before 1993). These increases are the result of many years of developing and implementing a continuum of preparation and retention programs.

Community-Institutional Relations↗
PubMed1999

People at risk of schizophrenia. Sample characteristics of the first 100 cases in the Edinburgh High-Risk Study.

BACKGROUND: The Edinburgh High-Risk Study is designed to explore the underlying pathogenesis of schizophrenia. AIMS: To establish the sample characteristics of the first 100 subjects in this study of young adults at risk of schizophrenia for genetic reasons, and to compare them with appropriate controls. METHOD: Details of the recruitment of the first 100 high-risk subjects aged 16-25 years into a prospective Scotland-wide study are given. Subjects and 30 age- and gender-matched normal controls were interviewed using the PSE, SADS-L and SIS and an unstructured psychiatric interview. RESULTS: Some significant differences emerged between the high-risk group and the control group, namely in previous psychiatric history (31 v. 6.3%), forensic contacts (19 v. 3.1%) and delinquent behaviour (20 v. 3.1%). There were also differences in some parameters from the SIS: childhood social isolation, interpersonal sensitivity, social isolation, suicidal ideation, restricted affect, oddness and disordered speech. CONCLUSIONS: These differences may represent increased risk of developing schizophrenia although their true significance will not be revealed until the cohort has been followed through the at-risk years.

Adult↗
PubMed1999

KRN8602 (MX2-hydrochloride): an active new agent for the treatment of recurrent high-grade glioma.

PURPOSE: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma. PATIENTS AND METHODS: Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score < or = 2) were treated with an intravenous bolus of 40 mg/m(2) KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles. RESULTS: A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting. CONCLUSION: KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.

Adolescent↗
PubMed1998

Central venous catheter infections treated with teicoplanin.

A novel way of using teicoplanin in situ to treat central venous catheters is described. Profound immunosuppression and the fact that the lines remain indwelling for long periods are two of the main reasons for these infections. In children it is also difficult to prevent these lines being played with, which increases the likelihood of infection. The different types of infection that can occur in a central venous catheter are described and the clinical definition of a catheter infection is provided. In an initial study, infective episodes in a small group of 11 children were treated successfully with in situ amikacin. Most pathogens were Gram-negative cocci. None of the catheters had to be removed, and catheter life was prolonged by a mean of 118 d. Due to the high incidence of Staphylococcus epidermidis in the initial study, in situ teicoplanin was assessed in a subsequent study. Over the course of 1 yr, 20 line infections occurred in 12 children. Empirical amikacin therapy was instituted and switched to teicoplanin once the pathogen was confirmed as Gram-positive. An antibiotic-heparin mixture was introduced into the line and left in place for 24 h, after which time it was replaced with fresh mixture until cultures were sterile. All pathogens were sensitive to teicoplanin, all infections were treated successfully and no catheters had to be removed. Overall, catheter life was prolonged by a mean of 136 d. It was concluded that in situ teicoplanin was effective and well tolerated for line infections (no side-effects were reported during the study). A minimum of 6 d therapy was recommended. The patients with less severe infections would have been suitable for treatment at home by their parents, district nurse or general practitioner (GP).

Adolescent↗
PubMed1997

Hox-type and non-Hox homeobox gene sequences in genomic DNA of the sea urchin Holopneustes purpurescens.

As a preliminary step in an analysis of Hox gene expression and radial body plan specification in sea urchin development, we amplified partial homeobox sequences in H. purpurescens by PCR using degenerate primers. The primers, HoxE and HoxF (Pendleton et al., 1993), spanned a highly conserved region of 82 nucleotides encompassing amino acids 21-47 of the homeodomain. Seven Hox-type homeobox sequences and two non-Hox homeobox sequences were identified. The seven Hox-type sequences were placed provisionally in Hox paralogous groups, one in paralogous group 3, three in paralogous groups 6-8 and three in paralogous groups 9 13. The non-Hox sequences had similarities with Xlox and Gbx homeobox genes.

Animals↗
PubMed1997

Applying empowerment in mental health practice.

The concept of empowerment has been widely discussed and its psychological and political meaning explored. However, it is rarely described in the context of nursing practice. This article focuses on the practice of empowering individuals with learning difficulties, within a secure setting. The ideas may be applied to any healthcare setting.

Hospitals, Psychiatric↗
PubMed1997

Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development.

Type III collagen is a fibrillar forming collagen comprising three alpha1(III) chains and is expressed in early embryos and throughout embryogenesis. In the adult, type III collagen is a major component of the extracellular matrix in a variety of internal organs and skin. Mutations in the COL3A1 gene have been implicated as a cause of type IV Ehlers-Danlos syndrome, a disease leading to aortic rupture in early adult life. To directly study the role of Col3a1 in development and disease, we have inactivated the Col3a1 gene in embryonic stem cells by homologous recombination. The mutated allele was transmitted through the mouse germ line and homozygous mutant animals were derived from heterozygous intercrosses. About 10% of the homozygous mutant animals survived to adulthood but have a much shorter life span compared with wild-type mice. The major cause of death of mutant mice was rupture of the major blood vessels, similar to patients with type IV Ehlers-Danlos syndrome. Ultrastructural analysis of tissues from mutant mice revealed that type III collagen is essential for normal collagen I fibrillogenesis in the cardiovascular system and other organs.

Animals↗
PubMed1997

Postoperative care and complications of damage control surgery.

Damage control procedures are being used with increasing frequency as the physiologic limits of the surgical patient are approached and recognized. These patients are returned to the SICU, where rapid restoration of circulating volume, normothermia, maintenance of oxygen delivery, and correction of transfusion-associated coagulopathy are essential to the success of the technique, which requires expeditious reoperation and completion of definitive surgical management. The potential need for early return to the operating room to control surgical bleeding must be recognized, as well as the difficulty in distinguishing between surgical bleeding and ongoing hemorrhage due to hypothermia and coagulopathy. Because the damage control technique is resource intensive and involves numerous personnel, organization and leadership are important to success.

Hemostatic Techniques↗
PubMed1997

The anthropometric assessment of dysmorphic features in schizophrenia as an index of its developmental origins.

BACKGROUND: Evidence suggests that schizophrenia may be a disorder with origins in early intrauterine mal-development. We have constructed a comprehensive anthropometric scale for the evaluation of dysmorphic features as an index of the nature and timing of developmental disturbance. METHOD: A detailed set of craniofacial and bodily measures was compiled and applied to 174 patients with schizophrenia and 80 matched control subjects. RESULTS: Patients had significantly higher scores on this scale and displayed multiple anomalies of the craniofacial region with an overall narrowing and elongation of the mid-face and lower face. Twelve craniofacial anomalies independently distinguished patients from controls and these variables correctly classified 95% of patients and 80% of control subjects. CONCLUSIONS: This new scale, while procedurally more exacting than the Waldrop scale, more clearly defines the topography of anomalies previously suspected in individuals with schizophrenia. These findings constitute direct evidence for disturbed craniofacial development in schizophrenia and indicate origins in the foetal period during which the characteristic human facial pattern evolves in close association with brain differentiation.

Abnormalities, Multiple↗
PubMed1996

Analysis of Mutator-induced mutations in the iojap gene of maize.

The recessive nuclear mutation iojap (ij) in maize produces striped plants with normal chloroplasts in green sectors and poorly developed chloroplasts in the white sectors. The ij mutation is also characterized by an array of additional phenotypic affects which suggests a pivotal role for Ij in chloroplast development. The Ij gene from maize has been isolated; however, the sequence has not provided information on the action of the Ij gene product. As an extension of the analysis of the Ij gene we have generated a number of independent transposon insertion mutations using the Robertson's Mutator (Mu). Insertions were found to be distributed throughout the 5' half of the gene and all showed a similar striping pattern to that of the original ij mutation, ij-ref. While several of the new mutant alleles produced ij-homologous transcripts none produced detectable levels of the Ij polypeptide product. Chloroplast development in some cells appears to be able to proceed in the absence of the Ij polypeptide.

Alleles↗